Cerebrovascular accident (CVA), also known as a stroke, is an acute neurologic injury whereby the blood supply to a part of the brain is interrupted, either by a clot in the artery or if the artery bursts. The result is that the part of the brain perfused by that artery no longer can receive oxygen carried by the blood and it dies (becomes necrotic) with cessation of function from that part of the brain. In addition to tissue death, hemorrhages also cause damage from physical impingement of blood on the brain tissue. Stroke is a medical emergency and can cause permanent neurologic damage or even death if not promptly diagnosed and treated. It is the third leading cause of death and adult disability in the US and industrialized European nations.[1]

In ischemic stroke, which occurs in approximately 85-90% of strokes, a blood vessel becomes occluded and the blood supply to part of the brain is totally or partially blocked. Ischemic stroke is commonly divided into thrombotic stroke, embolic stroke, systemic hypoperfusion (Watershed stroke), or venous thrombosis

In thrombotic stroke, a thrombus forming process develops in the affected artery and gradually the thrombus—built up clot—narrows the lumen of the artery and impedes blood flow to distal tissue. These clots usually form around atherosclerotic plaques. Since occlusion of the artery is gradual, onset of symptomatic thrombotic strokes is slower. A thrombus itself (even if non-occluding) can lead to an embolic stroke (see below) if the thrombus breaks off—at which point it is then called an "embolus." Thrombotic stroke can be divided into two types depending on the type of vessel the thrombus is formed on:

Small vessel disease involves the intracerebral arteries, branches of the Circle of Willis, middle cerebral artery stem, and arteries arising from the distal vertebral and basilar artery. Diseases that may form thrombus in the small vessels include (in descending incidence):

Lipohyalinosis (lipid hyaline build-up secondary to hypertension and aging) and fibrinoid degeneration. Stroke involving these vessels are known as lacunar infarcts

Microatheromas from larger arteries that extend into the smaller arteries (atheromatous branch disease)

Embolic stroke refers to the blockage of arterial access to a part of the brain by an embolus -- a travelling particle or debris in the arterial bloodstream originating from elsewhere. An embolus is most frequently a blood clot, but it can also be a plaque broken off from an atherosclerotic blood vessel or a number of other substances including fat, air, and even cancerous cells. Because an embolus arises from elsewhere, local therapy only solves the problem temporarily; source of the embolus must be identified. Because the embolic blockage is sudden in onset, symptoms usually are maximal at start. Also, symptoms may be transient as the embolus lyses and moves to a different location or dissipates altogether.
Embolic stroke can be divided into four categories:

Systemic hypoperfusion is the reduction of blood flow to all parts of the body. It is most commonly due to cardiac pump failure from cardiac arrest or arrhythmias, or from reduced cardiac output as a result of myocardial infarction, pulmonary embolism, pericardial effusion, or bleeding. Hypoxemia (low blood oxygen content) may precipitate the hypoperfusion. Because the reduction in blood flow is global, all parts of the brain may be affected, especially "watershed" areas --- border zone regions supplied by the major cerebral arteries. Blood flow to these area has not necessary stopped, but instead may have lessened to the point where brain damage occurs.

Veins in the brain function to drain the blood back to the body. When veins are occluded due to thrombosis, the draining of blood is blocked and the blood backs up, causing cerebral edema. This can result in both ischemic and hemorrhagic strokes. This commonly occurs in the rare disease sinus vein thrombosis.

A hemorrhagic stroke, or cerebral hemorrhage, is a form of stroke that occurs when a blood vessel in the brain ruptures or bleeds. Like ischemic strokes, hemorrhagic strokes interrupt the brain's blood supply because the bleeding vessel can no longer carry the blood to its target tissue. In addition, blood irritates brain tissue, disrupting the delicate chemical balance, and, if the bleeding continues, it can cause increased intracranial pressure which physically impinges on brain tissue and restricts blood flow into the brain. In this respect, hemorrhagic strokes are more dangerous than their more common counterpart, ischemic strokes. There are two types of hemorrhagic stroke: intracerebral hemorrhage, and subarachnoid hemorrhage.

Intracerebral hemorrhage (ICH) is bleeding directly into the brain tissue, forming a gradually enlarging hematoma (pooling of blood). It generally occurs in small arteries or arterioles and is commonly due to hypertension, trauma, bleeding disorders, amyloid angiopathy, illicit drug use (amphetamines and cocaine), and vascular malformations. The hematoma enlarges until pressure from surrounding tissue limits its growth, or until it decompresses by emptying into the ventricular system, CSF or the pial surface. A third of intracerebral bleed is into the brain's ventricles. ICH has a mortality rate of 44 percent after 30 days, higher than ischemic stroke or even the very deadly subarachnoid hemorrhage.[3]

Subarachnoid hemorrhage (SAH) is bleeding into the cerebrospinal fluid (CSF) of the subarachnoid space surrounding the brain. The two most common causes of SAH are rupture of aneurysms from the base of the brain and bleeding from vascular malformations near the pial surface. Bleeding into the CSF from a ruptured aneurysm occurs very quickly, causing rapidly increased intracranial pressure. The bleeding usually only lasts a few seconds but rebleeding is common. Death or deep coma ensues if the bleeding continues. Hemorrhage from other sources is less abrupt and may continue for a longer period of time. SAH has a 40% mortality over 30 day period.

The symptoms of stroke depend on the type of stroke and the area of the brain affected. Ischemic strokes usually only affect regional areas of the brain perfused by the blocked artery. Hemorrhagic strokes can affect local areas, but often can also cause more global symptoms due to bleeding and increased intracranial pressure.

In most cases, the symptoms affects one side of the body, from the neck downwards, excluding the face. The defect in the brain is usually on the opposite side of the body (depending on which part of the brain is affected). However, the presence of any one of these symptoms does not necessarily suggest a stroke, since these pathways also travel in the spinal cord and any lesion there can also produce these symptoms.

In addition to the above CNS pathways, the brainstem also consists of the 12 cranial nerves. A stroke affecting the brainstem therefore can produce symptoms relating to deficits in these cranial nerves:

Loss of consciousness, headache, and vomiting usually occurs more often in hemorrhagic stroke than in thrombosis because of the increased intracranial pressure from the leaking blood compressing on the brain.

If symptoms are maximal at onset, the cause is more likely to be a subarachnoid hemorrhage or an embolic stroke.

The symptoms of SAH occur abruptly due to the sudden onset of increased intracranial pressure. Often, patients complain of a sudden, extremely severe and widespread headache. The pain may or may not radiate down into neck and legs. Vomiting soon occurs after the onset of headache. Usually the neurologic exam is nonfocal --- meaning no deficits can be identified that attributes to certain areas of the brain --- unless the bleeding also occurs into the brain. The combination of headache and vomiting is uncommon in ischemic stroke.

If the symptoms resolve within an hour, or maximum 24 hours, the diagnosis is transient ischemic attack (TIA), and not a stroke. This syndrome may be a warning sign, and a large proportion of patients develop strokes in the future. Recent data indicate that there is about a ten to fifteen percent chance of suffering a stroke in the year following a TIA, with half of that risk manifest in the first month, and, further, with much of that risk manifest in the first 48 hours. The chances of suffering an ischemic stroke can be reduced by using aspirin or related compounds such as clopidogrel, which inhibit platelets from aggregating and forming obstructive clots; but, for the same reason, such treatments (slightly) increase the likelihood and effects of hemorrhagic stroke since they impair clotting.

It is important to identify a stroke as early as possible because patients who are treated earlier are more likely to survive and have better recoveries.

If a patient is suspected of having a stroke, emergency services should be contacted immediately. The patient should be transported to the nearest hospital that can provide a rapid evaluation and treatment with the latest available therapies targeted to the type of stroke. The faster these therapies are started for hemorrhagic and ischemic stroke, the chances for recovery from each type improves greatly. Quick decisions about medication and the need for surgery have been shown to improve outcome.

In increasing numbers of primary stroke centers, thrombolysis ("clot busting") is used to dissolve the clot and unblock the artery. However, there is a time constraint: the more time that goes by, the more brain that has irreversibly died. There is also a small risk of making the patient worse by causing bleeding. When used within the first 3 hours, thrombolysis improves the outcome in 1 of every 3.1 patients and worsens the outcome in 1 in every 32 patients. The routine use of thrombolysis is not approved beyond 3 hours. As an easily administered therapy that can be given at any hospital with a CAT scanner, thrombolysis is available at most hospitals in the US, but not where no institutional commitment to stroke care has occurred.

Another intervention for acute ischemic stroke is removal of the offending thrombus directly. This is accomplished by inserting a catheter into the femoral artery, directing it up into the cerebral circulation, and deploying a corkscrew-like device to ensnare the clot, which is then withdrawn from the body. In August 2004, the FDA cleared one such device, called the Merci Retriever.[4]

Whether thrombolysis is performed or not, the following investigations are required:

Other immediate strategies to protect the brain during stroke include ensuring that blood sugar is as normal as possible (such as commencement of an insulin sliding scale in known diabetics), and that the stroke patient is receiving adequate oxygen and intravenous fluids. The patient may be positioned so that his or her head is flat on the stretcher, rather than sitting up, since studies have shown that this increases blood flow to the brain. Additional therapies for ischemic stroke include aspirin (50 to 325 mg daily), clopidogrel (75 mg daily), and combined aspirin and dipyridamole extended release (25/200 mg twice daily).

It is common for the blood pressure to be elevated immediately following a stroke. Studies indicated that while high blood pressure causes stroke, it is actually beneficial in the emergency period to allow better blood flow to the brain.

Patients with bleeding into (intracerebral hemorrhage) or around the brain (subarachnoid hemorrhage), require neurosurgical evaluation to detect and treat the cause of the bleeding. Anticoagulants and antithrombotics, key in treating ischemic stroke, can make bleeding worse and cannot be used in intracerebral hemorrhage. Patients are monitored and their blood pressure, blood sugar, and oxygenation are kept at optimum levels.

Patients may have particular problems, such as complete or partial inability to swallow, which can cause swallowed material to pass into the lungs and cause aspiration pneumonia. The condition may improve with time, but in the interim, a nasogastric tube may be inserted, enabling liquid food to be given directly into the stomach. If swallowing is still unsafe after a week, then a percutaneous endoscopic gastrostomy (PEG) tube is passed and this can remain indefinitely.

Stroke rehabilitation can last anywhere from a few days to several months. Most return of function is seen in the first few days and weeks, and then improvement falls off. Complete recovery is unusual but not impossible. Most patients will improve to some extent.

Disability affects 75% of stroke survivors enough to decrease their employability.[5]
Stroke can affect patients physically, mentally, emotionally, or a combination of the three. The results of stroke vary widely depending on size and location of the lesion.[6]
Dysfunctions correspond to areas in the brain that have been damaged.

Some of the physical disabilities that can result from stroke include paralysis, numbness, pressure sores, pneumonia, incontinence, apraxia (inability to perform learned movements), difficulties carrying out daily activities, appetite loss, vision loss, and pain. If the stroke is severe enough, coma or death can result.

Emotional problems resulting from stroke can result from direct damage to emotional centers in the brain or from frustration and difficulty adapting to new limitations. Post-stroke emotional difficulties include anxiety, panic attacks, flat affect (failure to express emotions), mania, apathy, and psychosis.

30 to 50% of stroke survivors suffer post stroke depression (Post stroke depression), which is characterized by lethargy, irritability, sleep disturbances, lowered self esteem, and withdrawal.[7]
Depression can reduce motivation and worsen outcome, but can be treated with antidepressants.

Emotional lability, another consequence of stroke, causes the patient to switch quickly between emotional highs and lows and to express emotions inappropriately, for instance with an excess of laughing or crying with little or no provocation. While these expressions of emotion usually correspond to the patient's actual emotions, a more severe form of emotional lability causes patients to laugh and cry pathologically, without regard to context or emotion.[5]
Some patients show the opposite of what they feel, for example crying when they are happy.[8]
Emotional lability occurs in about 20% of stroke patients.

Cognitive deficits resulting from stroke include perceptual disorders, speech problems, dementia, and problems with attention and memory. A stroke sufferer may be perpetually unaware of his or her own disabilities or even the fact that he or she has suffered a stroke. In a condition called agnosia, or neglect, a patient is unable to see anything on the left or right side and is unaware of and unable to conceive of anything on the neglected side.

Up to 10% of all stroke patients develop seizures, most commonly in the week subsequent to the event; the severity of the stroke increased the likelihood of a seizure[9][10].

The most important risk factors for stroke are hypertension, heart disease, diabetes, and cigarette smoking. Other risks include heavy alcohol consumption, high blood cholesterol levels, illicit drug use, and genetic or congenital conditions. Family members may have a genetic tendency for stroke or share a lifestyle that contributes to stroke. Having had a stroke in the past greatly increases one's risk of future strokes.

One of the most significant stroke risk factors is advanced age. 95% of strokes occur in people age 45 and older, and two-thirds of strokes occur in those over the age of 65.-->[7][11] A person's risk of dying if he or she does have a stroke also increases with age. However, stroke can occur at any age, including in fetuses.

Sickle cell anemia, which can cause blood cells to clump up and block blood vessels, also increases stroke risk. Stroke is the second leading killer of people under 20 who suffer from sickle-cell anemia.[11]

Men are 1.25 times more likely to suffer CVAs than women,[11] yet 60% of deaths from stroke occur in women.[8] Since women live longer, they are older on average when they have their strokes and thus more often killed (NIMH 2002).[11] Some risk factors for stroke apply only to women. Primary among these are pregnancy, childbirth, menopause and the treatment thereof (HRT). Stroke seems to run in some families.

Prevention is an important public health concern. Identification of patients with treatable risk factors for stroke is paramount. Treatment of risk factors in patients who have already had strokes (secondary prevention) is also very important as they are at high risk of subsequent events compared with those who have never had a stroke. Medication or drug therapy is the most common method of stroke prevention. Aspirin (usually at a low dose of 75 mg) is recommended for the primary and secondary prevention of stroke. Treating hypertension, diabetes mellitus, smoking cessation, control of hypercholesterolemia, physical exercise, and avoidance of illicit drugs and excessive alcohol consumption are all recommended ways of reducing the risk of stroke.[1]

In patients who have strokes due to abnormalities of the heart, such as atrial fibrillation, anticoagulation with medications such as warfarin is often necessary for stroke prevention.[2]

Ischemic stroke occurs due to a loss of blood supply to part of the brain. Brain tissue ceases to function if deprived of oxygen for more than 60 to 90 seconds and after a few minutes will suffer irreversible injury possibly leading to a death of the tissue, i.e., infarction. Atherosclerosis may disrupt the blood supply by narrowing the lumen of blood vessels leading to a reduction of blood flow, by causing the formation of blood clots within the vessel, or by releasing showers of small emboli through the disintegration of atherosclerotic plaques. Embolic infarction occurs when emboli formed elsewhere in the circulatory system, usually in the heart, lodge in and occlude brain blood vessels.

Within the region of brain tissue affected by ischemia there is a spectrum of severity of the ischemia such that part of the tissue may immediately die while other parts may only be injured and could potentially recover. The ischemia area where tissue might recover is referred to as the ischemic penumbra.

As oxygen or glucose becomes depleted in ischemic brain tissue the production of high energy phosphate compounds such as adenine triphosphate (ATP), fails leading to failure of energy dependent processes necessary for tissue cell survival. This sets off a series of interrelated events that result in cellular injury and death. Among these is the loss of membrane ion pump function that leads to electrolyte imbalances in brain cells, the release of excitatory neurotransmitters, which have toxic effects in excessive concentrations, the release of oxygen free radicals that react with and damage a number of cellular elements, and the failure of mitochondria, which can lead further toward energy depletion and may trigger cell death due to apoptosis..<!--

These processes are the same for any type of ischemic tissue and are referred to collectively as the ischemic cascade. However, brain tissue is especially vulnerable to ischemia since it has little respiratory reserve and is completely dependent on aerobic metabolism, unlike most other organs.

Brain tissue survival can be improved to some extent if one or more of these processes is inhibited. Drugs that reduce oxygen free radicals, inhibit apoptosis, or inhibit excitotoxic neurotransmitters, for example, have been shown experimentally to reduce tissue injury due to ischemia. Agents that work in this way are referred to as being neuroprotective. However, no neuroprotective agents have been shown to be effective in humans..[11]

In addition to injurious effects on brain cells, ischemia and infarction can result in loss of structural integrity of brain tissue and blood vessels, partly through the release of matrix metalloproteases, which are zinc and calcium dependent enzymes that break down collagen, hyaluronic acid, and other elements of connective tissue. Other proteases also contribute to this process. The loss of vascular structural integrity results in a breakdown of the protective blood brain barrier that contributes to cerebral edema, which can cause secondary progression of the brain injury.

As is the case with any type of brain injury, the immune system is activated by cerebral infarction and may under some circumstances exacerbate the injury caused by the infarction. Inhibition of the inflammatory response has been shown experimentally to reduce tissue injury due to cerebral infarction, but this has not proved out in clinical studies.

Hemorrhagic strokes result in tissue injury by causing compression of tissue from an expanding hematoma or hematomas. This can distort and injure tissue. In addition, the pressure may lead to a loss of blood supply to affected tissue with resulting infarction, and the blood released by brain hemorrhage appears to have direct toxic effects on brain tissue and vasculature.[11]

Over 2,400 years ago, Hippocrates (460 to 370 BC) was first to describe the phenomenon of sudden paralysis, which we now know is caused by stroke. Apoplexy, from the Greek word meaning "struck down with violence,” first appeared in Hippocratic writings to describe stroke symptoms.[12][13]

In 1658, in his Apoplexia, Johann Jacob Wepfer (1620-1695) identified the cause of hemorrhagic stroke when he suggested that people who had died of apoplexy had bleeding in their brains.[12][11]
Wepfer also identified the main arteries supplying the brain, the vertebral and carotid arteries, and identified the cause of ischemic stroke when he suggested that apoplexy might be caused by a blockage to those vessels.[11]